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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2001-8-24
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pubmed:abstractText |
Arsenic trioxide has recently been shown to inhibit growth and induce apoptosis in acute promyelocytic leukemia (APL), but little is known about the molecular mechanisms mediating these effects. Here we demonstrate that treatment of promonocytic U937 cells with arsenic trioxide leads to G2/M arrest which was associated with a dramatic increase in the levels of cyclin B and cyclin B-dependent kinase and apoptosis. We further show that apoptosis occurs after bcl-2 phosphorylation and caspase-3 activation followed by cleavage of PARP and PLC-gamma1 degradation and DNA fragmentation. The arsenic trioxide-induced apoptosis could be blocked by the protein synthesis inhibitor cycloheximide. In addition, pretreatment of U937 cells with the DNA polymerase inhibitor aphidicolin also blocked apoptosis, but did not cause the arrest of cells in the G2/M phase. The findings suggest that arsenic trioxide exerts its growth-inhibitory effects by modulating expression and/or activity of several key G2/M regulatory proteins. Furthermore, arsenic trioxide-mediated G2/M arrest correlates with the onset of apoptosis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Arsenicals,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Oxides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/arsenic trioxide
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
726-34
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11520058-Antineoplastic Agents,
pubmed-meshheading:11520058-Apoptosis,
pubmed-meshheading:11520058-Arsenicals,
pubmed-meshheading:11520058-Caspase 3,
pubmed-meshheading:11520058-Caspases,
pubmed-meshheading:11520058-Cell Division,
pubmed-meshheading:11520058-Cycloheximide,
pubmed-meshheading:11520058-Enzyme Activation,
pubmed-meshheading:11520058-G2 Phase,
pubmed-meshheading:11520058-Growth Inhibitors,
pubmed-meshheading:11520058-Humans,
pubmed-meshheading:11520058-Leukemia, Promyelocytic, Acute,
pubmed-meshheading:11520058-Mitosis,
pubmed-meshheading:11520058-Monocytes,
pubmed-meshheading:11520058-Myeloid Progenitor Cells,
pubmed-meshheading:11520058-Oxides,
pubmed-meshheading:11520058-Phosphorylation,
pubmed-meshheading:11520058-Protein Synthesis Inhibitors,
pubmed-meshheading:11520058-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11520058-U937 Cells
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pubmed:year |
2001
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pubmed:articleTitle |
Arsenic trioxide induces G2/M growth arrest and apoptosis after caspase-3 activation and bcl-2 phosphorylation in promonocytic U937 cells.
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pubmed:affiliation |
Department of Immunology, School of Medicine, Keimyung University, Taegu, South Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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